Clinicopathological significance of WT1 expression in ovarian cancer: a possible accelerator of tumor progression in serous adenocarcinoma

Abstract

Recently, oncogenic potential of the WT1 gene has been proposed in some human solid tumors and leukemias. Although previous studies have shown the frequent expression of the WT1 protein in ovarian serous adenocarcinomas (OSAs), its clinicopathologic significance is still unclear. We immunohistochemically examined the expression status of WT1 in 119 OSAs and analyzed the correlation of the intensity of WT1 immunoreactivity with the level of WT1 mRNA expression by quantitative real-time polymerase chain reaction, clinicopathologic variables, expression of p53, Bcl-2, and Ki-67 labeling index (LI). Of 119 OSAs, nuclear WT1 immunoreactivity was positive in 99 (83%), of which 44 (44%) and 55 (56%) exhibited high and low WT1 immunoreactivities, respectively. The quantitative WT1 mRNA levels were significantly correlated with the intensity of WT1 immunoreactivity (P < 0.05). In comparison with WT1-negative OSAs, the WT1-positive OSAs showed a higher grade (P = 0.007), advanced stage (P = 0.018), and higher Ki-67 LI (P < 0.001). Additionally, high WT1 immunoreactivity was correlated with a higher grade (P = 0.003), Ki-67 LI (P = 0.012), Bcl-2 expression (P = 0.003), and poorer patient outcome (5-year survival, 36.5 vs 63.8%, P = 0.008 by log-rank test). The WT1 protein may be an accelerator of the progression of OSA.

Wilms' tumor 1 (WT1) expression and prognosis in solid cancer patients: a systematic review and meta-analysis

“…A total of 29 studies 9 11 12 13 14 15 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 with 32 datasets and 4090 patients assessing the relationship between WT1 expression and prognosis of solid tumors were initially identified ( Figure 1 ), and the details of selected studies are shown in Table 1 . Twenty-one datasets evaluated carcinoma (9 for ovarian cancer, 5 for breast cancer, 3 for non-small-cell lung cancer [NSCLC], 2 for endometrial cancer, 1 for colorectal cancer and 1 for hepatocellular carcinoma) and 11 datasets evaluated non-carcinoma (2 for soft tissue sarcoma).…”

Tissue Biomarkers in Prognostication of Serous Ovarian Cancer following Neoadjuvant Chemotherapy

“…Studies on Bcl2 in relation to prognosis are not uniform. Some studies have failed to demonstrate any significant correlation with survival [57]. On the other hand few studies have shown high levels of Bcl2 expression to be associated with lower chances of response to chemotherapy and a shorter survival [58, 59].…”

RhoB mediates antitumor synergy of combined ixabepilone and sunitinib in human ovarian serous cancer

“…3 At the molecular level, high-grade ovarian serous carcinomas are genetically unstable and frequently have TP53 mutations, loss of BRCA1 or BRCA2 function, and/or amplification of oncogenes such as PRKCI, NOTCH3, EGFR, HER2, c-MYC and WT1 along with activation of several signaling pathways including ras/raf/MAP kinase and PI3 kinase/Akt pathways. 4–7 Low levels or altered expression of apoptosis-regulating proteins such as Bcl-2, BAX, survivin and RhoB are also reported in these tumors. 4, 8, 9 Reports suggest that in ovarian cancer, there is enhanced angiogenic-signaling pathway and a higher expression of PDGFRα, PDGFRβ and c-kit with autocrine or paracrine stimulation of the receptors by their respective ligands.…”